Modeling defective interfering virus therapy for AIDS: conditions for DIV survival (No DIV Interference)
Model Status
This CellML model has been built from the differential expressions in Nelson and Perelson's 1995 paper for the initial model without DIV interference (equations 1-10). This file is known to run in OpenCell and COR, and uses the parameters values in Tables 1, 2, and 3 of the paper. One of the units (for the variable theta) has been changed from micro_L (in the paper), to per_micro_L, to be dimensionally consistent. Parameters in years are represented in day equivalents. The CellML model simulation will replicate the graph traces in figure 2 of the paper. Note that in the paper, some figures are scaled logarithmically.
Model Structure
ABSTRACT: The administration of a genetically engineered defective interfering virus (DIV) that interferes with HIV-1 replication has been proposed as a therapy for HIV-1 infection and AIDS. The proposed interfering virus, which is designed to superinfect HIV-1 infected cells, carries ribozymes that cleave conserved regions in HIV-1 RNA that code for the viral envelope protein. Thus DIV infection of HIV-1 infected cells should reduce or eliminate viral production by these cells. The success of this therapeutic strategy will depend both on the intercellular interaction of DIV and HIV-1, and on the overall dynamics of virus and T cells in the body. To study these dynamical issues, we have constructed a mathematical model of the interaction of HIV-1, DIV, and CD4+ cells in vivo. The results of both mathematical analysis and numerical simulation indicate that survival of the engineered DIV purely on a peripheral blood HIV-1 infection is unlikely. However, analytical results indicate that DIV might well survive on HIV-1 infected CD4+ cells in lymphoid organs such as lymph nodes and spleen, or on other HIV-1 infected cells in these organs.
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| Schematic illustration of the main features of the model. |
The original paper reference is cited below:
Modeling defective interfering virus therapy for AIDS: conditions for DIV survival, Nelson G, Perelson A, 1995, Mathematical Biosciences, 125, 127-153. PubMed ID: 7881191